Evidence map›Paper›PMID 26917578›Full record

ArticleThorax2016

Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12.

Victoria E Jackson, Ioanna Ntalla, Ian Sayers, Richard Morris, Peter Whincup, Juan-Pablo Casas, Antoinette Amuzu, Minkyoung Choi, Caroline Dale, Meena Kumari and 30 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Thorax, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. A systematic analysis of protein-altering exonic variants in chronic obstructive pulmonary disease.American journal of physiology. Lung cellular and molecular physiology · 2021
    Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. What will Happen in the World of COPD 2030?Turkish thoracic journal · 2019
    Review
  16. Review
  17. Review
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

40 authors at 18 institutions in 3 countries.

Victoria E JacksonDepartment of Health Sciences, University of Leicester, Leicester, UK.
Ioanna NtallaDepartment of Health Sciences, University of Leicester, Leicester, UK William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Ian SayersDivision of Respiratory Medicine, University of Nottingham, Queen's Medical Centre, Nottingham, UK.
Richard MorrisSchool of Social & Community Medicine, University of Bristol, Bristol, UK Department of Primary Care & Population Health, UCL, London, UK.
Peter WhincupPopulation Health Research Institute, St George's, University of London, London, UK.
Juan-Pablo CasasUniversity College London, Farr Institute of Health Informatics, London, UK Cochrane Heart Group, London, UK.
Antoinette AmuzuDepartment of Non-communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
Minkyoung ChoiDepartment of Non-communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
Caroline DaleDepartment of Non-communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
Meena KumariISER, University of Essex, Colchester, Essex, UK Department of Epidemiology and Public Health, UCL, London, UK.
Jorgen EngmannInstitute of Cardiovascular Science, UCL, London, UK.
Noor KalshekerSchool of Life Sciences, University of Nottingham, Nottingham, UK.
Sally ChappellSchool of Life Sciences, University of Nottingham, Nottingham, UK.
Tamar Guetta-BaranesSchool of Life Sciences, University of Nottingham, Nottingham, UK.
Tricia M McKeeverDivision of Epidemiology and Public Health, Nottingham City Hospital, University of Nottingham, Nottingham, UK.
Colin N A PalmerCardiovascular and Diabetes Medicine, School of Medicine, University of Dundee, Dundee, UK.
Roger TavendaleCardiovascular and Diabetes Medicine, School of Medicine, University of Dundee, Dundee, UK.
John W HollowayHuman Development & Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK NIHR Southampton Respiratory Biomedical Research Unit, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton, UK.
Avan A SayerMRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton, UK.
Elaine M DennisonMRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK Victoria University, Wellington, New Zealand.
Cyrus CooperMRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton, UK.
Mona BafadhelRespiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0002-9993-2478
Bethan BarkerInstitute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK National Institute for Health Research Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Chris BrightlingInstitute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK National Institute for Health Research Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Charlotte E BoltonNottingham Respiratory Research Unit, University of Nottingham, City Hospital Campus, Nottingham, UK.
Michelle E JohnNottingham Respiratory Research Unit, University of Nottingham, City Hospital Campus, Nottingham, UK.
Stuart G ParkerInstitute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK.
Miriam F MoffatDepartment of Molecular Genetics and Genomics, National Heart and Lung Institute, Imperial College London, London, UK.
Andrew J WardlawInstitute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK National Institute for Health Research Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Martin J ConnollyFreemasons' Department of Geriatric Medicine, University of Auckland, New Zealand.
David J PorteousGeneration Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Blair H SmithDivision of Population Health Sciences, University of Dundee, Dundee, UK.
Sandosh PadmanabhanInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Lynne HockingInstitute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Kathleen E StirrupsWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK Department of Haematology, University of Cambridge, Cambridge, UK.
Panos DeloukasWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
David P StrachanPopulation Health Research Institute, St George's, University of London, London, UK.
Ian P HallDivision of Respiratory Medicine, University of Nottingham, Queen's Medical Centre, Nottingham, UK.
Martin D TobinDepartment of Health Sciences, University of Leicester, Leicester, UK National Institute for Health Research Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Louise V WainDepartment of Health Sciences, University of Leicester, Leicester, UK.
University of Nottingham · GBUniversity of Leicester · GBSouthampton General Hospital · GBLondon School of Hygiene & Tropical Medicine · GBUniversity of Dundee · GBQueen Mary University of London · GBSt George's, University of London · GBEdinburgh Cancer Research · GBFarr Institute · GBImperial College London · GBNewcastle Hospitals - Campus for Ageing and Vitality · GBUniversity College London · GBUniversity of Aberdeen · GBUniversity of Auckland · NZUniversity of Bristol · GBUniversity of Essex · GBUniversity of Glasgow · GBUniversity of Oxford · GB

Funding

British Heart Foundation PG/13/66/30442British Heart Foundation RG/08/013/25942British Heart Foundation RG/13/16/30528Chief Scientist Office CZD/16/6/4Department of Health PDF-2013-06-052Medical Research Council G0400491Medical Research Council G0601369Medical Research Council G0902313Medical Research Council G1000861Medical Research Council G1001799Medical Research Council MC_PC_12010Medical Research Council MC_QA137853Medical Research Council MC_U147585819Medical Research Council MC_U147585824Medical Research Council MC_U147585827Medical Research Council MC_UP_A620_1014Medical Research Council MC_UP_A620_1015Medical Research Council MC_UU_12011/1Medical Research Council MC_UU_12011/2Medical Research Council MR/N01104X/1Versus Arthritis 19583Wellcome Trust
6 · The paper itself

Abstract

backgroundSeveral regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants.

objectiveTo determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated with the risk of COPD and severity of airflow limitation.

methods3226 current or former smokers of European ancestry with lung function measures indicative of Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 COPD or worse were genotyped using an exome array. An analysis of risk of COPD was carried out using ever smoking controls (n=4784). Associations with %predicted FEV1 were tested in cases. We followed-up signals of interest (p<10(-5)) in independent samples from a subset of the UK Biobank population and also undertook a more powerful discovery study by meta-analysing the exome array data and UK Biobank data for variants represented on both arrays.

resultsAmong the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in MOCS3 (rs7269297, pdiscovery=3.08×10(-6), preplication=0.019) and a rare SNP in IFIT3, which emerged in the meta-analysis (rs140549288, pmeta=8.56×10(-6)). In the meta-analysis of % predicted FEV1 in cases, the strongest association was shown for a splice variant in a previously unreported region, SERPINA12 (rs140198372, pmeta=5.72×10(-6)). We also confirmed previously reported associations with COPD risk at MMP12, HHIP, GPR126 and CHRNA5. No associations in novel regions reached a stringent exome-wide significance threshold (p<3.7×10(-7)).

conclusionsThis study identified several associations with the risk of COPD and severity of airflow limitation, including novel regions MOCS3, IFIT3 and SERPINA12, which warrant further study.

Indexed as

Polymorphism, Single NucleotideAgedAirway ObstructionExomeFemaleForced Expiratory VolumeGenome-Wide Association StudyGenotypeHumansIntracellular Signaling Peptides and ProteinsMaleMiddle AgedNucleotidyltransferasesPulmonary Disease, Chronic ObstructiveRisk AssessmentSerpinsIFIT3 protein, humanIntracellular Signaling Peptides and ProteinsMOCS3 protein, humanNucleotidyltransferasesSERPINA12 protein, humanSerpinsSulfurtransferasesCOPD epidemiologyTobacco and the lung

Identifiers

PMID26917578
PMCPMC4893124
OpenAlexW2277205211

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.